As many as 1 in 3 adults (up to 72 million people) in the United States has high blood pressure. Hypertension can lead to coronary heart disease, heart failure, stroke, kidney failure, and other health problems, and is attributed to 7 million deaths worldwide each year.
Blood pressure has a genetic component and hypertension runs in families. Attempts to identify genes associated with blood pressure have met with limited success but now an international research team says they have identified a number of unsuspected genetic variants associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (high blood pressure), suggesting potential avenues of investigation for the prevention or treatment of hypertension.
In a genome-wide association study (GWAS), researchers scanned millions of common genetic variants of individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium to find variants associated with blood pressure and hypertension. This extensive resource includes white men and women from the Framingham Heart Study, Atherosclerosis Risk in Communities study, Cardiovascular Health Study, the Rotterdam Study, the Rotterdam Extension Study, and the Age, Gene/Environment Susceptibility Reykjavik Study.
The investigators identified a number of genetic variants or single-nucleotide polymorphisms (SNPs) associated with SBP, DBP, and hypertension. When they jointly analyzed their findings with those from the GWAS of over 34,000 participants in the Global BPgen Consortium (whose results are presented in an accompanying paper in the same issue of Nature Genetics), they identified 11 genes showing significant associations across the genome: four for SBP, six for DBP, and one for hypertension.
"Large scale genome-wide association studies are providing a number of important insights into identifying genes that play a role in diseases with major public health impact," said Dr. Daniel Levy, first author of the study and director, the NHLBI's Framingham Heart Study and Center for Population Studies. "We have identified eight key genes, few of which would have been on anyone's short list of suspected blood pressure genes until now."
The international research team included Cornelia M. van Duijn, Ph.D., Erasmus Medical Center, Rotterdam, the Netherlands; Aravinda Chakravarti, Ph.D., Johns Hopkins University; Bruce Psaty, M.D., Ph.D., University of Washington; and Vilmundur Gudnason, M.D., Ph.D., Icelandic Heart Association, Kopayogur, Iceland.
The blood pressure genes include ATP2B1 which encodes PMCA1, a cell membrane enzyme that is involved in calcium transport; CACNB2, which encodes part of a calcium channel protein; and CYP17A1 which encodes an enzyme that is necessary for steroid production. One detected variant is within the gene SH2B3 and has been associated with autoimmune diseases, hinting that pathways involved with the immune response may influence blood pressure.
Blood pressure is measured in millimeters of mercury (mm Hg), and expressed with two numbers, for example, 120/80 mm Hg. The first number (systolic pressure) is the pressure when the heart beats while pumping blood. The second number (diastolic pressure) is the pressure in large arteries when the heart is at rest between beats.
Researchers found that the top 10 gene variants, or SNPs, for systolic and diastolic blood pressure were each associated with around a 1 and 0.5 mm Hg increase in systolic and diastolic blood pressure, respectively. The prevalence of hypertension increased as the number of variants increased.
People who carry very few blood pressure genetic risk variants have blood pressure levels that are several mm Hg lower than those who carry multiple risk variants. In practical terms this is enough to increase the risk for cardiovascular disease. A prolonged increase in DBP of only 5 mm Hg is associated with a 34 percent increase in risk for stroke and a 21 percent increase of coronary heart disease.
The research was funded by National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health grants and contracts and was also supported by the National Human Genome Research Institute (NHGRI), National Center for Research Resources (NCRR), National Institute on Aging (NIA), and the NIH Roadmap.
The analysis of over 29,000 participants is being presented at the American Society of Hypertension, Inc. scientific meeting on May 8, 2009, and was published online in Nature Genetics.
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